Objective:To predict the short-term postoperative recurrence status of patients with refractory temporal lobe epilepsy (TLE) by analyzing preoperative 18F-FDG PET images and patients′ clinical characteristics based on deep residual neural network (ResNet). Methods:Retrospective analysis was conducted on preoperative 18F-FDG PET images and clinical data of 220 patients with refractory TLE (132 males and 88 females, age 23.0(20.0, 30.2) years)) in the First Affiliated Hospital of Jinan University between January 2014 and June 2020. ResNet was used to perform high-throughput feature extraction on preprocessed PET images and clinical features, and to perform a postoperative recurrence prediction task for differentiating patients with TLE. The predictive performance of ResNet model was evaluated by ROC curve analysis, and the AUC was compared with that of classical Cox proportional risk model using Delong test. Results:Based on PET images combined with clinical feature training, AUCs of the ResNet in predicting 12-, 24-, and 36-month postoperative recurrence were 0.895±0.073, 0.861±0.058 and 0.754±0.111, respectively, which were 0.717±0.093, 0.697±0.081 and 0.645±0.087 for Cox proportional hazards model respectively ( z values: -3.00, -2.98, -1.09, P values: 0.011, 0.018, 0.310). The ResNet showed best predictive effect for recurrence events within 12 months after surgery. Conclusion:The ResNet model is expected to be used in clinical practice for postoperative follow-up of patients with TLE, helping for risk stratification and individualized management of postoperative patients.

Objective:To determine incidence of seasonal influenza virus infection in the community and to analyze the factors influencing seasonal influenza virus infection.Methods:This study recruited residents aged 6-59 years to build a cohort in 15 villages/streets in Macheng city in November 2019. Meanwhile, a cross-sectional baseline survey was conducted immediately to collect sera, information on demographics and child protection knowledge, behaviors, as well as attitudes using a questionnaire from the participants enrolled in the cohort (i.e., before the influenza epidemic season). In July 2020, a cross-sectional follow-up survey was conducted to collect sera once again (i.e., after the influenza season). Paired sera from the two cross-sectional surveys were tested for influenza virus-specific antibodies by hemagglutination inhibition (HI) test or micro-neutralization (MN) test using a circulating representative strain of each subtype/lineage of influenza virus as the test antigen. The infections with influenza virus subtype/lineage was confirmed if there was a four-fold or more increase in titers of antibodies against circulating representative strain of the subtype/lineage of influenza virus. Factors influencing infection with influenza A (H3N2) and B/Victoria viruses were analyzed using univariable and multivariable logistic regression.Results:In November 2019, 800 study participants were enrolled in the cohort, including 340 children aged 6-17 years and 460 adults aged 18-59 years; 605 study participants (including 224 children and 381 adults) were followed up in July 2020 and their paired sera were obtained before and after the influenza season. 25.3% (153/605) of the participants were confirmed to be infected with at least one subtype/lineage of seasonal influenza virus by HI and MN tests. The overall incidence of influenza viruses of all subtypes/lineages in children was 44.2% (95% CI: 37.6%-50.8%) which was significantly higher than the incidence of 14.1% in adults (95% CI: 10.7%-17.7%). Children had the highest incidence of influenza A (H3N2) virus infection, followed by B/Victoria. MN or HI antibody titers in A (H3N2)[ OR=0.88 (95% CI: 0.84-0.93)] and B/Victoria[ OR=0.97 (95% CI: 0.95-0.99)] before the influenza season were significantly associated with whether children were infected with that subtype/lineage of influenza virus. Conclusions:The residents aged 6-59 years in Macheng city had a substantial incidence of seasonal influenza virus infection during the influenza season from winter 2019 to spring 2020. Notably, almost half of children aged 6-17 years have been infected with seasonal influenza virus. Higher titers of HI/MN antibodies against seasonal influenza virus before the influenza season would be likely to reduce the risk of infection with influenza A (H3N2) and B/Victoria.

Objective:To explore the efficacy of adjuvant chemotherapy and adjuvant immunotherapy combined chemotherapy after radical cystectomy for muscle-invasive bladder cancer (MIBC) with high recurrence risk (pT 2 with positive lymph nodes, and pT 3-4a with or without positive lymph nodes). Methods:A retrospective analysis was conducted on clinical data of 217 patients with bladder cancer admitted to Tianjin Medical University Second Hospital from August 2016 to January 2022. Among them, 183 were male (84.3%) and 34 were female (15.7%), with an average age of (67.3±8.6) years old. All 217 patients underwent radical cystectomy with pelvic lymph node dissection. Based on postoperative adjuvant treatment, the patients were divided into an observation group (147 cases, 67.7%) and a treatment group (70 cases, 32.3%). The observation group and treatment group had similar demographic and pathological characteristics. The age of the observation group and treatment group was (67.4±9.0) years and (66.3±7.6) years, respectively ( P=0.14). The postoperative pathological stages T 2 with lymph node positivity were observed in 8 cases (5.4%) in the observation group and 6 cases (8.6%) in the treatment group. For stages T 3-4awith lymph node positivity, there were 34 cases (23.1%) in the observation group and 18 cases (25.7%) in the treatment group. And there were 105 cases (71.5%) in the observation group and 46 cases (65.7%) in the treatment group of stages T 3-4a without lymph node positivity, respectively( P>0.05). Tumor diameter ≥3 cm was found in 118 cases (80.3%) in the observation group and 54 cases (77.1%) in the treatment group ( P>0.05), while tumor diameter <3 cm was observed in 29 cases (19.7%) in the observation group and 16 cases (22.9%) in the treatment group ( P>0.05).In the treatment group, 36 patients (16.6%) received postoperative chemotherapy with gemcitabine (1 000 mg/m 2, days 1 and 8) and cisplatin (75 mg/m 2, days 2 to 4) (chemotherapy group), while 34 patients (15.7%) received postoperative immunotherapy with checkpoint inhibitors (intravenous infusion of sintilimab 200 mg, terlizumab 200 mg, or toripalimab 240 mg on day 1) in combination with albumin-bound paclitaxel (200 mg on day 2)(immunotherapy combined chemotherapy group). The age of the chemotherapy group and immunotherapy combined chemotherapy group was (66.8±8.4) years and (65.8±6.8) years, respectively ( P>0.05). Postoperative pathological stages T 2 with lymph node positivity were observed in 3 cases (8.3%) in the chemotherapy group and 3 cases (8.8%) in the immunotherapy combined chemotherapy group ( P>0.05). For stages T 3-4awith lymph node positivity, there were 6 cases (16.7%) in the chemotherapy group and 12 cases (35.3%) in the immunotherapy combined chemotherapy group. And there were 27 cases (75.0%) in the observation group and 19 cases (55.9%) in the treatment group of stages T 3-4a without lymph node positivity, respectively( P>0.05). Lymph node involvement was seen in 9 cases (25.0%) in the chemotherapy group and 15 cases (44.1%) in the immunotherapy combined chemotherapy group ( P>0.05). Tumor diameter ≥3 cm was found in 30 cases (83.3%) in the chemotherapy group and 10 cases (29.4%) in the immunotherapy combined chemotherapy group ( P>0.05), while tumor diameter <3 cm was observed in 6 cases (16.7%) in the chemotherapy group and 24 cases (70.6%) in the immunotherapy combined chemotherapy group ( P>0.05). Kaplan-Meier method and multivariate Cox regression test were used to analyze the overall survival (OS) at 1 and 3 years in the observation group and treatment group, as well as the disease-free survival (DFS) at 1 and 3 years in the chemotherapy group and immunotherapy combined chemotherapy group. Additionally, common adverse events were evaluated and compared between the chemotherapy group and immunotherapy combined chemotherapy group based on the criteria published by the U. S. Department of Health and Human Services. Results:The median follow-up time in this study was 18.4 (8.2, 34.7) months. The median follow-up time in the observation group and treatment group was 19.0 (8.3, 35.2) months and 17.5 (7.9, 33.2) months, respectively. The 1-year survival rate was significantly higher in the treatment group compared to the observation group (90.0% vs. 76.2%, χ2=6.92, P=0.009). Similarly, the 3-year survival rate was significantly higher in the treatment group compared to the observation group (82.9% vs. 57.8%, χ2=13.22, P<0.01). The median OS was 35.9 months in the observation group and was not reached in the treatment group, with a statistically significant difference ( HR=2.51, 95% CI 1.36-4.65, P=0.003).In the chemotherapy group and immunotherapy combined chemotherapy group, the median follow-up time was 10.7 (7.4, 22.1) months and 14.4 (6.3, 40.7) months, respectively. The 1-year disease-free survival rate was significantly higher in the immunotherapy combined chemotherapy group compared to the chemotherapy group (91.2% vs. 67.6%, χ2=4.60, P=0.032). The 3-year disease-free survival rate was significantly higher in the chemotherapy group compared to the immunotherapy combined chemotherapy group (88.2% vs. 55.6%, χ2=8.37, P=0.004). The median DFS was 27.7 months in the chemotherapy group and was not reached in the immunotherapy combined chemotherapy group, with a statistically significant difference ( HR=3.39, 95% CI 1.46-7.89, P=0.016).The treatment group had complications classified as follows: 140 cases of grade 1, 39 cases of grade 2, 8 cases of grade 3, 2 cases of grade 4, and 0 case of grade 5 adverse reactions. In the chemotherapy group and the immunotherapy combined chemotherapy group, there were both 5 cases with adverse reactions of grade 3 or higher. Specifically, in the chemotherapy group, there were 2 cases of anemia, 2 cases of decreased platelet count, and 1 case of decreased neutrophil count. In the immunotherapy combined chemotherapy group, there was 1 case of anemia, 1 case of decreased platelet count, and 2 cases of decreased neutrophil count. Additionally, there was 1 case with elevated gamma-glutamyltransferase (γ-GT) in the immunotherapy combined chemotherapy group. The incidence of adverse events of grade 3 or higher in the chemotherapy group and immunotherapy combined chemotherapy group was 13.9% and 14.7%, respectively, with no statistically significant difference( χ2=0.01, P=0.922). Conclusions:Adjuvant therapy significantly prolongs the overall survival in high risk of recurrence for MIBC patients after radical cystectomy. For patients intolerant to platinum-based chemotherapy or refusing platinum-based adjuvant chemotherapy, immunotherapy with checkpoint inhibitors combined with albumin-bound paclitaxel can be considered as an effective and well-tolerated adjuvant treatment after radical cystectomy.

SIRT6 belongs to the conserved NAD⁺-dependent deacetylase superfamily and mediates multiple biological and pathological processes. Targeting SIRT6 by allosteric modulators represents a novel direction for therapeutics, which can overcome the selectivity problem caused by the structural similarity of orthosteric sites among deacetylases. Here, developing a reversed allosteric strategy AlloReverse, we identified a cryptic allosteric site, Pocket Z, which was only induced by the bi-directional allosteric signal triggered upon orthosteric binding of NAD⁺. Based on Pocket Z, we discovered an SIRT6 allosteric inhibitor named JYQ-42. JYQ-42 selectively targets SIRT6 among other histone deacetylases and effectively inhibits SIRT6 deacetylation, with an IC₅₀ of 2.33 μmol/L. JYQ-42 significantly suppresses SIRT6-mediated cancer cell migration and pro-inflammatory cytokine production. JYQ-42, to our knowledge, is the most potent and selective allosteric SIRT6 inhibitor. This study provides a novel strategy for allosteric drug design and will help in the challenging development of therapeutic agents that can selectively bind SIRT6.

Maili moxibustion can alleviate cancer pain, reduce bone marrow suppression, alleviate gastrointestinal reaction of chemotherapeutic drugs, alleviate cancer-related fatigue, inhibit neurotoxic reaction, improve quality of life and prolong patients' survival. It plays therapeutic effects by regulating immunity, inhibiting tumor cell proliferation and regulating tumor microenvironment. The researches of Maili moxibustion for tumor focus on reducing the toxic or side effects of radiotherapy or chemotherapy. In the future, we should continue to study the combination of Maili moxibustion and other therapies on the treatment of tumor.

Objective: To investigate the changes of plasma protein expression profile in hyperhomocysteinemia rats and the protective effect of highly expressed angiopoietin 1 in plasma on endothelial cells. Methods: The hyperhomocysteinemia animal model was established. The difference in plasma protein content was analyzed by label-free protein spectroscopy. The effects of homocysteine and angiopoietin 1 on endothelial cell migration and proliferation were detected by wound healing and CCK-8 proliferation assay. Results: The results of protein profiling showed that 5 proteins were significantly up-regulated and 17 proteins were significantly down-regulated in the plasma of hyperhomocysteinemia rats, among which angiopoietin 1 was significantly up-regulated. In endothelial cells in the superior mesenteric artery of rats, treatment with 30 or 50 μmol/L homocysteine for 24 h significantly inhibited the migration and proliferation. Angiopoietin 1(600 ng/ml) significantly reduced the migration and proliferation of endothelial cells inhibited by 30 μmol/L homocysteine, but had no significant effect on the migration and proliferation of endothelial cells inhibited by 50 μmol/L homocysteine. Conclusion Hyperhomocysteinemia can significantly affect the protein expression profile in plasma. Angiopoietin 1 in plasma can compensate for the damage of vascular endothelial migration and proliferation function caused by homocysteine in a certain concentration range.

Objective:To explore the relationship between body mass index (BMI), waist circumference (WC) and the risk for ischemic stroke in adults in China.Methods:A total of 36 632 adults were selected from 60 surveillance areas (25 urban surveillance areas and 35 rural surveillance areas) in China Chronic Disease Surveillance Project in 2010 for a follow up study from 2016 to 2017 based on the baseline data in 2010. The follow up was completed for 27 762 adults. Cox proportional hazard regression model was used to analyze the association of body mass index and waist circumference with the risk for ischemic stroke in different populations. The death and hypercholesterolemia cases were excluded by sensitivity analysis.Results:A total of 26 907 adults were included in the analysis. During the follow up period, 1 128 ischemic stroke events were observed (491 in men and 637 in women). After adjusting the related confounding factors and taking normal BMI/normal WC group as the reference, the risk for ischemic stroke increased by 50% in normal BMI/abdominal obesity group ( HR=1.50, 95% CI:1.07-2.08), 51% in overweight/abdominal obesity group ( HR=1.51, 95% CI:1.20-1.91), 46% in obesity/abdominal obesity group ( HR=1.46, 95% CI:1.09-1.96), and 63% in normal BMI/abdominal obesity group ( HR=1.63, 95% CI:1.12-2.38), 56% in overweight/abdominal obesity group ( HR=1.56, 95% CI: 1.20-2.03) and 45% in obesity/abdominal obesity group ( HR=1.45, 95% CI: 1.05-2.01) respectively in men and in men with CVD risk factors. There was no increased risks in the overweight/normal WC group. The risk increased by 40% in overweight/abdominal obesity group ( HR=1.40, 95% CI:1.15-1.72) and 46% in obesity/abdominal obesity group ( HR=1.46, 95% CI:1.16-1.83), and 35% in overweight/abdominal obesity group ( HR=1.35, 95% CI:1.08-1.69) and 30% in obesity/abdominal obesity group ( HR=1.30, 95% CI:1.01-1.67) respectively in women and women with CVD risk factors. There were no risk increases in overweight/normal WC group and normal BMI/abdominal obesity group. Sensitivity analysis results showed no change. Conclusion:Overweight/obesity with abdominal obesity or abdominal obesity alone could increase the risk for stroke in men, and overweight/obesity with abdominal obesity could increase the risk for ischemic stroke in women; suggesting that BMI and WC should be used jointly to evaluate obesity in population for weight control to prevent ischemic stroke.

Objective:To analyze the association between waist-to-height ratio and the overall and type specific incidence of stroke in adults in China.Methods:A total of 36 632 people were selected from 60 surveillance sites (25 in urban area and 35 in rural area) in China Chronic Disease Surveillance Project in 2010. The China Chronic Disease Surveillance Project data in 2010 were used as baseline data. A total of 27 762 people were followed up from 2016 to 2017. Cox proportional risk regression model was used to analyze the risk ratio of waist-to-height ratio for the overall and type specific incidence of stroke. Subgroup analyses were performed based on baseline characteristics such as age and sex, and sensitivity analysis was performed by excluding those who died and those with diabetes at baseline survey.Results:A total of 27 112 subjects were included in the stroke analysis, and 1 333 stroke events were observed. A total of 26 907 subjects were included in the ischemic stroke analysis, and 1 128 ischemic stroke events were observed. A total of 25 984 subjects were included in the hemorrhagic stroke analysis, and 205 cases of hemorrhagic stroke were observed. After adjusting for relevant confounders and taking group with waist-to-height ratio of 0-0.45 as a reference, the stroke analysis indicated that in groups with waist-to-height ratio of 0.46-0.49, 0.50-0.54 and ≥0.55 the risk for stroke increased by 21% ( HR=1.21, 95% CI:1.00-1.46), 26% ( HR=1.26, 95% CI:1.04-1.53) and 60% ( HR=1.60, 95% CI:1.29-1.99) respectively. Subgroup analysis revealed that age specific waist-to-height ratio had modification effect on the risk for stroke (interaction P=0.001). Ischemic stroke analysis indicated that in groups with waist-to-height ratio of 0.46-0.49, 0.50-0.54 and ≥0.55 the risk for ischemic stroke increased by 30% ( HR=1.30, 95% CI: 1.05-1.60), 33% ( HR=1.33, 95% CI: 1.07-1.64) and 61% ( HR=1.61, 95% CI: 1.26-2.05) respectively. Subgroup analysis revealed that age specific waist-to-height ratio had modification effect on the risk for ischemic stroke (interaction P=0.024). Hemorrhagic stroke analysis indicated that in group with waist-to-height ratio of ≥0.55 the risk for hemorrhagic stroke increased by 73% ( HR=1.73, 95% CI: 1.02-2.94), but the differences in the risk increase in groups with waist-to-height ratio of 0.46-0.49 and 0.50-0.54 were not significant. The sensitivity analysis showed no changes. Conclusions:In the prevention and control of stroke by body weight control, it is necessary to take waist to height ratio as one of the indicators of body weight control. Particular attention needed to be paid to the people aged <50 years with waist-to-height ratio of ≥0.55 as well as those with waist-to-height ratio of <0.5 (i.e., 0.46-0.49).

Objective:To compare the efficacy and safety of ultrasound-guided percutaneous translumial septal myocardial ablation in dogs using laser and radiofrequency.Methods:Twelve healthy adult Beagle dogs (males or females) were randomly divided into two groups, namely, group laser and group radiofrequency (6 dogs each group). Under ultrasound guidance, laser fiber or radiofrequency ablation needle was respectively inserted into the basal and middle segments of the interventricular septa via the percutaneous transapical approach to perform ablation. The Beagle dogs received radiologic examination, laboratory tests and pathological detection before ablation, immediately after ablation, at 1 week after ablation, and at 1 month after ablation, respectively. The efficacy and safety of the two ablation procedures were compared.Results:All dogs survived after ablation. The peak gradient of LVOT decreased immediately after ablation using either laser or radiofrequency ( P<0.05), but it increased at 1 week after ablation than before ( P<0.05). At 1 month after ablation, no significant differences were found in the peak gradient of LVOT compared with that before surgery ( P<0.05). The interventricular septum thickness was increased immediately after ablation using either laser or radiofrequency than before ( P<0.05), but it decreased at 1 week and at 1 month after surgery than before ( P<0.05). The ablation zone using radiofrequency was slightly larger than that of using laser[(372.50±69.06)mm 3 vs (116.65±20.15)mm 3, P<0.001], and the surgical time of the former was significantly shorter than that of using laser [(56.00±3.22)s vs (260.00±65.39)s, P<0.05)]. Conclusions:Ultrasound-guided percutaneous translumial septal myocardial ablation is feasible, safe and effective using either laser or radiofrequency. Comparatively speaking, radiofrequency ablation is more simple and convenient.

Objective To summarize the clinical characteristics of hepatic lymphoepithelioma-like carcinoma,and to explore the diagnosis and treatment strategies of hepatic lymphoepithelioma-like carcinoma.Methods A retrospectively analysis on 13 patients with liver lymphoepithelioma-like carcinoma in Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,between March 2005 and May 2019 were carried out.Results 8 cases were male,5 were female,median age was 45years (27 to 68 y).There were 8 cases of intrahepatic cholangiocytic lymphoepithelioma-like carcinoma,4cases of hepatocytic lymphoepithelioma-like carcinoma,and 1 case of mixed hepatocytic and cholangiocytic lymphoepithelioma-like carcinoma.All patients received partial hepatectomy and postoperative comprehensive treatment.The patients were followed from 6 months to 7 years.Only one patient died,and the other patients were all in a tumor-free state.Conclusion Primary hepatic lymphoepithelioma-like carcinoma is a rare liver cancer.It is confirmed mainly by pathological examination and immunohistochemistry.With surgery as the main treatment,prognosis is usually fair.